Antimycobacterials

Question 1

Isoniazid (INH)

Answer 1

Decreases synthesis of mycelia acids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite.
Mycobacterium tuberculosis. Only agent used as solo prophylaxis against TB.
Neurotoxicity, hepatotoxicity, different INH half lives in fast/slow acetylators. Pyridoxine (B6) can prevent neurotoxicity and lupus.

Question 2

Rifampin

Answer 2

Rifamycin.
Inhibits DNA-dependent RNA polymerase.
Mycobacterium tuberculosis. Delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B.
Minor hepatotoxicity and drug interactions (increases P-450). Orange body fluids (non-hazardous). More CYP450 stimulation than rifabutin.

Question 3

Rifabutin

Answer 3

Rifamycin.
Inhibits DNA-dependent RNA polymerase.
Mycobacterium tuberculosis. Delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B.
Minor hepatotoxicity and drug interactions (increases P-450). Orange body fluids (non-hazardous). Less CYP450 stimulation than rifampin.

Question 4

Pyrazinamide

Answer 4

Uncertain mechanism. Thought to acidify intracellular environment via conversion to pyrazinoic acid. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.
Mycobacterium tuberculosis
Hyperuricemia, hepatotoxicity.

Question 5

Ethambutol

Answer 5

Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
Mycobacterium tuberculosis.
Optic neuropathy (red/green color blindness).